KR101599447B1 - A composition and use thereof in the treatment of anal rhagades - Google Patents

Abstract

The present invention relates to a composition comprising at least one hibiscus protein extract and / or at least one beta glucan or salt thereof.
The present invention also relates to the use of the composition for the treatment of anal dentition.

Description

≪ Desc / Clms Page number 1 > COMPOSITION AND USE THEREOF IN THE TREATMENT OF ANAL RHAGADES &

The present invention relates to a composition comprising at least one hibiscus protein extract and / or at least one beta-glucan. The present invention also relates to the use of the composition for the treatment of anal dentition.

Anal dentition is usually located in the posterior commissure of the lower anal canal and is an ulcer of the anal canal with contraction of the internal sphincter.

Laceration of the anal mucosa at the dental site causes mild bleeding during defecation. Contraction of the internal sphincter causes high tension in the anal canal, which causes pain (major symptom). Pain is strong and intense, especially during and after bowel movements (up to 3-4 hours), allowing the patient to avoid bowel movements and thus become stiff, thus aggravating the problem.

Anal dentition can occur to individuals of all ages, regardless of gender, but it has been experimentally proven that individuals at the age of 20-40 are most at risk. Anal dentition is the second most common cause of rectal examination after hemorrhoids. In fact, the incidence of anal dentition in outpatient clinics is 9-12%. According to data from the 2009 annual report of the SICCR (Italian Society of Colorectal Surgery), a total of 5199 rectal cracks were observed, and 37% (1924) of the patients underwent surgery.

Although clinical signs of dentition are well known, the etiology is still unclear.

According to epidemiologic theories, the triggering factor can be represented by the difficulty of defecation and trauma caused by the passage of hard edges. This results in strong, persistent pain, which in turn leads to an inhibition and delay of stimulation, which in turn makes the mutation harder and worsens the symptoms.

Thus, trauma can cause dentition, but it can be cured if other factors do not intervene. The first of these is the persistent high tension of the inner sphincter and the second is the localized anemia symptom at the level of the rectum. In fact, the rectal tube where the dentition is located is supplied with blood by the lower rectal artery. However, relative arterial deficits are observed in post-drilling of the rectum tube in 85% of individuals with dentition (angiographic results). Furthermore, blood flow decreases with increasing anal pressure, and vice versa. Therefore, hypertension and anemia are closely interrelated phenomena.

Anal dentition can be distinguished by rapid formation and chronic type.

Rapid casting is characterized in that the surface of the anoderm (ie, the epithelial layer of the anal canal) is radially shaped and exhibits smooth edges and rosy light. This usually involves very severe pain. Rapid casting can have a tendency to cause adhesion, but it often recurs or develops into a chronic type.

If the teeth appear for less than 6 weeks, they are considered to be grade castings. Acute anal dentition was cured spontaneously in 70% of the subjects. Therapeutic treatment for acute dentition is a conservative form, and surgery is actually performed only if treatment fails.

Chronic anal dentition is characterized by the radial shape of the anal skin inside, which swells up to white with a soft sphincter of fibrous tissue around it. It is often accompanied by the appearance of a prominent anal lobe, a small, soft protrusion of the anal canal epithelium. It is considered chronic when anal dentition lasts more than six weeks. Chronic dentition is naturally cured only up to 20%.

Numerous studies have been conducted to establish a better therapeutic approach in view of the very low cure rates of chronic anal dentition, which are either conservative or surgical.

Acute anal dentition can be treated in a conservative manner by removing the seizure of the internal sphincter that causes high tension.

Conservative treatment suggests fiber-rich diets, high liquid intake, and very thorough and delicate local hygiene. When dentition is associated with constipation, the use of fibrin is recommended to soften the lubricant and / or stool.

The medical treatment method is performed to reduce the high tension of the anal sphincter and to facilitate the healing of the dentition.

Recent studies on the physiopathology of anal sphincter have revealed that nitrogen monoxide is an inhibitor of anal sphincter tension. So-called "reversible chemical sphincterotomy" can be performed by locally applying a trinitroglycerin (TNG) ointment that can relax the anal sphincter.

An average of 58% of cases were cured within 2 months of treatment, with 11 to 46.2% recurring.

The most common complication of this treatment was headache, with an average of 57% in the cases, sometimes requiring discontinuation of treatment.

In addition, pharmacological treatment of dentition suggests injecting botulinum toxin as a soft sphincter of the intestine to reduce the tension of the anal sphincter to heal the dentition. Usually, relaxation paralysis occurs several hours after toxin injection, which tends to last 3-4 months.

Dental scar formation occurs in 2-96% of cases within 2 months after treatment, of which 30% recur.

However, in 18% of cases, this treatment represents a very serious side effect, that is, temporary incontinence.

Another therapeutic alternative is to administer calcium channel blockers. This reduces maximum sphincter pressure at rest, but has serious adverse side effects in patients with heart disease and diabetes.

Surgical treatment is required if satisfactory response is not obtained by conservative therapy or medication, or if the dentition recurs and worsens over time. This may require a variety of surgical techniques, although with varying degrees. A modern version of anal incision (now considered obsolete), defined as mechanical anal sphincteroclasia, can be performed. This technique uses a rubber balloon inserted into the anal canal and inflated to a controlled pressure. The sphincter is expanded by it for a few minutes (about 5 minutes), and the sphincter and tension are overcome. A significant proportion of the incidence and duration of incontinence occur with varying degrees (8 - 35%).

The "gold standard" treatment of anal dentition is "lateral sphincterotomy". It is defined as "open" when a skin incision is made with exposure of the sphincter, and "closed" when performed without a sphincter exposure.

All of these techniques can guarantee a high rate of patient healing (> 90% within 2 months of treatment).

The most serious complications are incidence of urinary incontinence, which in most cases is temporary (8.9% - 13.0% of cases) and in some cases may be persistent (0.6% - 6.9%).

This surgery may be controlled by a controlled internal sphincter lateral incision that can be adjusted according to the degree of dentition, the length of the sphincter and the degree of high tensions measured. This may reduce persistence or recurrence of dentition and failure due to complications associated with urinary incontinence.

In view of the broad nature of this pathology, which is most often accompanied by severe and severe pain, there is a strong need for a new therapeutic method to treat or at least alleviate pain in anal dentition.

Particularly, clinical studies in this field have shown that the need for surgery to cause urinary incontinence, which is a non-physiological condition that brings serious inconvenience to individuals, especially from an psycho-social point of view, [0004] BACKGROUND OF THE INVENTION [0005] [0002] Significant attention has been focused on identifying novel therapies for conservative forms, e.g., pharmacological protocols,

The present invention relates to compositions comprising at least one hibiscus protein extract and at least one beta glucan or a salt thereof, as described in the claims, suitable for this context.

The invention also relates to the use of a composition comprising at least one hibiscus protein extract and / or at least one beta-glucan or salt thereof for the treatment of anal dentition as described in the claims.

Indeed, the Applicant has surprisingly found that by using at least one hibiscus protein extract and / or at least one beta glucan in the anal dentition, it is possible to ameliorate a symptomatic or non-symptomatic disease caused by anal dentition immediately upon use ≪ / RTI >

In particular, the Applicant has found that this composition can reduce the high tensions of the inner sphincter by exerting a restoring action on the local epithelium, and can reduce pain associated with defecation by preferably relaxing the anal canal smooth muscle.

The first aspect of the present application relates to a protein extract of at least one hibiscus, which is preferably selected from the group consisting of Hybiscus esculentus, commonly known as < RTI ID = 0.0 > Okra or Abelmoschus esculentus, The present invention relates to an extract of a plant belonging to the genus Malvaceae.

The at least one hibiscus protein extract is preferably at least one protein fraction, more preferably at least one soluble protein fraction, derived from hibiscus seeds. In particular, the protein fraction is derived from hibiscus seeds, preferably from the flour of hibiscus seeds, more preferably from defatted seeds and / or flour.

The protein extract or the protein fraction is preferably a protein hydrolyzate, preferably obtained from a natural protein. The hydrolyzate can be obtained by enzymatic hydrolysis and / or chemical hydrolysis. Or the hydrolyzate is obtained by in vivo transformation.

In the context of the present invention, in vivo transformation refers to the process of making a substance more hydrolyzable, for example by hydrolysis, oxidation, reduction or conjugation, thereby introducing a hydrophilic group or exposing it to a hydrophilic group.

In one embodiment, the hydrolyzate is a mixture of oligopeptides. Preferably the hydrolyzate is a binder, more preferably a mixture with dextrin. In a preferred embodiment, the ratio of the hydrolyzate to the binder is preferably 1: 1.

Mixtures of preferred oligopeptides for the purposes of the present invention are commercially available under the trade name Myoxinol ( ^TM ).

The concentration of at least one protein extract of the hibiscus ranges from 0.1 to 10%, preferably from 0.4 to 5%.

A second aspect of the invention relates to beta glucans, preferably carboxymethyl beta-glucans and / or salts thereof, more preferably sodium carboxymethyl beta-glucans.

The concentration of the beta-glucan is in the range of 0.004 to 0.4%, preferably in the range of 0.02 to 0.08%.

The ratio of the extract of at least one hibiscus protein to the at least one beta glucan is preferably 50 - 10: 1, more preferably 35 - 20: 1.
The composition of the present invention is preferably characterized by having a pH in the range of 5 to 8, more preferably in the range of 5.5 to 6.5. In order to adjust the pH of the composition of the present invention, a pH adjusting agent (defined as a pH adjusting agent) may be used, and preferably a basic substance such as triethanolamine may be used.

The concentration of the modifier is in the range of 0.03 to 1%, preferably in the range of 0.1 to 0.6%.

In a preferred embodiment, the composition of the present invention, preferably formulated in a gel cream (i.e., gel emulsion), preferably has a viscosity in the range of 5000 to 30000 mPas, more preferably in the range of 7000 to 25000 mPas .

The compositions of the present invention may further comprise at least one pharmaceutically acceptable excipient that is useful in the manufacture of a composition and is generally biologically safe and non-toxic, or a compound acceptable for pharmaceutical or cosmetic use.

The excipient may be at least one modulating agent, preferably a moisturizing, blocking or emollient for skin or hair.
In particular, the regulator is selected from the group consisting of dimethicone or dimethylpolysiloxane, preferably linear glycerin, almond oil (preferably Prunus amygdalus dulcis oil), phenyl trimethicone, borage oil (preferably Borago officinalis seed oil) / Mucilage, preferably Malva sylvetris mucilage, panthenol, calendula extract, preferably an extract of Calendula officinalis , ethylhexyl glycerin, caprylyl glycol, aspartic acid, maltodextrin and glyceryl stearate .

The concentration of the modifier is preferably in the range of 15 to 35%, more preferably in the range of 20 to 25%.

Preferably, the concentration of the dimethicone or dimethylpolysiloxane ranges from 2.5 to 10%, more preferably from 3.5 to 7%.

Preferably, the concentration of glycerin ranges from 2.5 to 10%, more preferably from 3.5 to 7%.

Preferably, the concentration of the almond oil is in the range of 2 to 8%, more preferably 3 to 6%.

Preferably, the concentration of the phenyl trimethicone ranges from 1 to 4%, more preferably from 1.5 to 3%.

Preferably, the concentration of the borage oil ranges from 1 to 4%, more preferably from 1.5 to 3%.

Preferably, the concentration of the extract is from 1 to 4%, more preferably from 1.5 to 3%.

Preferably, the concentration of the panthenol ranges from 0.5 to 2%, more preferably from 0.75 to 1.5%.

Preferably, the concentration of the calendula extract is in the range of 0.1 to 0.4%, more preferably 0.15 to 0.3%.

Preferably, the concentration of caprylylglycol ranges from 0.1 to 0.4%, more preferably from 0.15 to 0.3%.

Preferably, the concentration of the maltodextrin ranges from 0.1 to 0.4%, more preferably from 0.15 to 0.3%.

Preferably, the concentration of the glyceryl stearate is in the range of 0.4 to 1.8%, more preferably 0.5 to 1.2%.

Preferably, the concentration of ethylene hexyl glycerin ranges from 0.05 to 0.2%, more preferably from 0.75 to 0.15%.

Preferably, the concentration of the aspartic acid is in the range of 0.0002 to 0.001%, more preferably 0.0003 to 0.0008%.

The excipient may also be a surfactant, preferably an emulsifying or cleaning surfactant. More preferably, the surfactant is selected from the group consisting of cetyl alcohol, cetyl (20) OE, or ceteth-20, stearyl (20) OE or stearase-20 and PEG-75 stearate.

The concentration of the surfactant is preferably in the range of 1 to 3%, more preferably 1.2 to 2%.

The concentration of cetyl alcohol is preferably in the range of 0.5 to 1%, the concentration of PEG-75 stearate is preferably in the range of 0.2 to 1%, and the concentration of Ceteth-20 or Stearath- And preferably in the range of 0.05 to 0.25%.

In addition, the excipient may be a preservative, preferably phenoxyethanol, or the excipient may be an antioxidant, preferably a tocopherol and glycyrrhiza glabra dry extract.

The concentration of the preservative is preferably in the range of 0.3 to 1%, more preferably 0.5 to 1%, and the concentration of the antioxidant is preferably in the range of 0.1 to 1%, more preferably 0.2 to 0.6% .

The excipient is also preferably a binder selected from dextrins, or the excipient may be a stabilizer, preferably an emulsion stabilizer, more preferably a crosslinked acrylic copolymer, and the excipient is a chelating agent, May be triisodium ethylenediamine disuccinate.

Preferably, the concentration of the binder is in the range of 0.5 to 2%, more preferably 0.75 to 1.5%, and the concentration of the chelating agent is preferably 0.01 to 0.08%, more preferably 0.02 to 0.06% , And the concentration of the stabilizer is preferably in the range of 0.15 to 0.6%, more preferably 0.2 to 0.4%.

The% of the concentration of the various components of the composition of the present invention should be regarded as weight / weight percent, and thus is for 100 grams of product.

The composition of the present invention is prepared in a solvent which is water and / or 1,2-hexanediol.

With this solvent, the composition is made to a final weight of 100%.

Another aspect of the present invention relates to a composition for topical application formulated as a topically formulated formulation, especially a cream, a gel cream, a gel, an oil, an emulsion, a gel emulsion (emulgel), an ointment, a spray or a suppository or stick (such as a coconut butter stick) To compositions of the invention.

Alternatively, the compositions of the present invention may be formulated for oral use, preferably as lozenges, tablets or granules, or for injectable use.

The composition may be formulated to release the active ingredient contained therein rapidly after administration or to delay and / or control the release of the active ingredient.

Another aspect of the invention relates to the use of a composition comprising at least one hibiscus extract and at least one beta glucan or salt thereof as a medicament.

Another aspect of the invention relates to the use of a composition comprising at least one hibiscus extract and / or at least one beta-glucan or a salt thereof for the treatment of anal dysgenesis, preferably acute anal dentition.

In a preferred embodiment, the compositions of the invention are administered locally, preferably at least once a day, more preferably at least twice a day.

Administration is preferably carried out for at least one week, more preferably for at least two weeks. The best results are obtained by treatment for at least 20 days.

The compositions of the present invention may be administered alone or in combination with adjuvants or adjuvants effective for the treatment of dentition.

Alternatively, the compositions may be used in conjunction with other methods and / or protocols for the treatment of anal dentition. A preferred example of such a method and / or protocol relates to the use of an analyst expander.

Another aspect of the invention relates to a process for preparing a composition comprising at least one hibiscus protein extract and / or at least one beta-glucan according to the invention.

The method includes the following steps.

(i) the controlling agent, preferably the blocking and / or sedative controlling agent, and / or the surfactant, preferably the emulsifying and / or cleaning surfactant, in the range of 70 to 90 占 폚, more preferably in the range of 75 to 80 占 폚 ;

(ii) mixing a solvent, a modifier, preferably a humectant, a chelating agent and / or a stabilizing emulsifier with the raw material dissolved according to step (i);

(iii) adding at least one hibiscus extract to the mixture according to step (ii);

(iv) adding at least one beta-glucan to the mixture of step (iii).

The hibiscus extract according to step (iii) is preferably dissolved in water, more preferably purified water. The dissolution is preferably carried out at a temperature of from 40 to 60 캜, more preferably from 50 to 55 캜.

The at least one beta-glucan according to step (iv) is preferably added as an aqueous solution of 1-5% aqueous solution (percent by weight / weight percent), more preferably 1.5-2.5%. The temperature of the mixture to which the at least one beta-glucan is to be added is preferably in the range of 35 to 45 ° C, more preferably in the range of 32 to 37 ° C.

The mixing of the components of the composition of the present invention is preferably continued until a semi-finished product is obtained. The semi-finished product can be immediately used or packaged.

Another aspect of the invention relates to a kit comprising a composition comprising at least one hibiscus protein extract and / or at least one beta glucan or salt thereof.

Preferably, the composition of the kit is formulated as a cream, gel, or emulsion gel. More preferably, the kit comprises at least one, preferably at least 20, dispensers (e.g., squeeze tubes) containing the composition of the present invention in a preferably preliminary dosage. The dispenser is preferably disposable and more preferably provided with an applicator that is preferably used with the dispenser to facilitate application of the composition on the anal dentition to be treated.

Preferably, the dispenser is of a size capable of delivering a sufficient amount of the pre-dose of the composition.

Example

Methods of preparing compositions of the present invention in gel cream form

The raw material is introduced into the mixer according to the method and amount provided in the preparation.

Prior to mixing with the other components of the manufacturing method, the raw materials required in the melting process are melted in the molten portion at a temperature of 75 to 80 캜.

The temperature of the mixture is then lowered to 50-55 DEG C, the micoxycinol dissolved in hot purified water (50-55 DEG C) is added, and then beta-glucan (2% solution) is added to other components which do not require melting or solubilization . These components are added at a temperature below 35 ° C and mixing continues until a semi-finished product for use / packaging is obtained.

Formulation example

Examples of compositions formulated with a gel / cream and functionalized for use in the present invention are set forth in Table 1 below.

INCI EU % Purified water Until it is 100 glycerin 5.0000% Dimethylpolysiloxane 5.0000% Sweet Almond Oil (Prunus dolcis) 4.0000% Malva sylvestris 2.0000% Borago officinalis (Borago officinalis) 2.0000% Phenyl trimethicone 2.0000% d-Panthenol 1.0000% dextrin 0.8625% Hydrolyzed hibiscus extract 0.8625% Cetyl alcohol 0.8625% Glyceryl stearate 0.8625% Phenoxyethanol 0.5000% Stearate (75) OE 0.4250% Crosslinked acrylic copolymer 0.3000% Triethanolamine 0.3000% Calendula dry extract 0.2000% Licorice dry extract 0.2000% Cetyl (20) OE 0.1750% Stearyl (20) OE 0.1750% Tocopherol 0.1000% Ethylhexyl glycerin 0.0800% Carboxymethylbeta-glucan sodium salt 0.0300%

Assessment of rectal mucosal irritation by the composition of the present invention

Rectal mucosal irritation of the composition of the present invention in gel cream form was evaluated. The test was performed on six male albino rabbits.

Specifically, 3 rabbits were treated with 1 ml of the gel / cream composition of the present invention, and 3 rabbits were treated with 1 ml of saline (control). The treatment was provided by injecting a gel / cream (treatment sample) or saline (control sample) directly into the rectum of each animal using a soft catheter.

The rectal mucosa of each animal was observed daily to detect the presence of irritation phenomena such as erythema and / or scab.

After 24 hours from the last day of treatment, animals were sacrificed and samples of rectal mucosa of animals were taken for histological examination.

The detected microscopic responses were evaluated based on the data presented in Table 3.

reaction Numerical classification 1. epithelium Normally, 0 Cell degeneration or flattening One deterioration 2 Focal erosion 3 Whole body erosion 4 2. Leukocyte infiltration ( Hi  Power field) absence 0 Minimum (less than 25) One Some (26 to 50) 2 Usually (51 to 100) 3 Above 100 in excess) 4 3. Encephalopathy absence 0 at least One slightly 2 usually 3 Prominent, vascular rupture 4 4. Edema absence 0 at least One slightly 2 usually 3 splendor 4

In the macroscopic examination, the inflammatory response detected in the application area of the animals treated with the test composition was compared to that detected in the control animals.

The scores of microscopic evaluation of all animals treated with the test composition were added and divided by the number of animals to determine the average stimulation potential for the treated group. The same calculation was made for the control group.

In a microscopic evaluation of control tissue, score 9 may be indicative of a potential pathology, or it may be indicative of trauma from administration in a control animal. Both situations may require retesting for the same high scores in the treatment group or in other animals in the control group. The mean value of the control group was subtracted from the mean value of the test group to obtain the stimulation index.

The stimulation index is shown in Table 4.

Stimulation index Average score Explanation 0 none 1-4 at least 5-8 slightly 9-11 middle 12-16 serious

The results of the macroscopic evaluation are shown in Table 5.

Treatment Rabbit No . Average (x) 1199 1200 1201 0 0 0 0.00 0 0 0 0.00 0 0 0 0.00 Control rabbits No Average (x) 1202 1203 1204 0 0 0 0.00 0 0 0 0.00 0 0 0 0.00

No abnormal symptoms due to treatment with the test composition or saline were detected in the animals.

Table 6 summarizes the microscopic test results.

parameter Treatment Rabbit No 1199 1200 1201 epithelium 0 0 0 Leukocyte infiltration 0 0 0 Venous congestion 0 0 0 edema 0 0 0 parameter Control rabbits No 1202 1203 1204 epithelium 0 0 0 Leukocyte infiltration 0 0 0 Venous congestion 0 0 0 edema 0 0 0

Based on the results of Table 6, the composition according to the invention shows the possibility of stimulation corresponding to zero. The rectal stimulation index is actually zero.

In conclusion, the composition of the present invention can be regarded as unstimulated against rectal mucosa.

Delayed Inflammation Test - The guinea pig maximization test with the composition of the present invention GPMT )

The test was carried out on white female guinea pigs, in particular 10 animals (group 1) were treated with the composition of the invention and 5 animals constituted the control (group 2).

Group 1 was treated with a gel / cream form of composition and Group 2 was treated with saline.

 Group 1 contained 1-50: 50 (v: v) of a 50:50 (v / v) diluted test product with a stable emulsion of Freund's complete adjuvant (FCA) and saline and a stable emulsion of FCA and saline ) Intradermal injection (Sample 1).

Group 2 animals were treated with a 1-50: 50 (v / v) intradermal injection (sample 2) of a stable emulsion of saline and Freund's complete adjuvant (FCA). Saline was diluted 50:50 (v / v) with a stable emulsion of FCA and saline (50%).

The animals used in this study were randomly selected among the appropriate animals available at the time of the study. The animals were divided into groups of up to 5 cages per cage.

An area of about 50 cm 2 was shaved in animals and the like 24 hours before the treatment.

The test consists of an induction phase and a challenge phase.

On day 0 of induction, three pairs of intradermal injections containing 0.1 ml of each of the samples described above were applied on both sides of the midline of the scapula region of all animals.

On the seventh day of induction, after intradermal injection, 1 ml of sample was applied locally to all animals under sealed dressing. The dispensing was done randomly for the scanning position. The dressing was kept for 48 hours. The same procedure was performed on control animals using saline instead of the composition of the present invention.

For the conductors, on day 21, 1 ml of the diluted test composition was topically treated under seal dressing on the right side for all guinea pigs. The dressing was maintained for 24 hours.

Skin responses on all animals were evaluated on day 23 (24 hours after dressing removal) and on day 24 (48 hours after dressing removal). The intensity of erythema and edema was evaluated according to the Magnusson and Cligman scale as shown in Table 7.

reaction Numerical scale No visible change 0 Occasional or partial erythema One Moderate fusogenic erythema 2 Severe erythema and edema 3

In the test group, one or more McGerson and Kleemann score values generally show sensitization when a value of less than 1 is observed in the control animals.

If a value of more than one is observed in the control animals, the response of the test animals above the most severe response of the control animals is presumed to be due to sensitization.

If the response is unclear, it is necessary to re-run to see the results of the primary challenge. Test results are presented as the frequency of positive responses to challenge of test and control animals.

The results are summarized in Table 8.

The composition Tested  animal Time after dressing removal 24 hours 48 hours One 0 0 2 0 0 3 0 0 4 0 0 5 0 0 6 0 0 7 0 0 8 0 0 9 0 0 10 0 0 Control animals
Time after dressing removal 24 hours 48 hours One 0 0 2 0 0 3 0 0 4 0 0 5 0 0

The results show that no abnormality was detected in both the animals treated with this composition and the control animals, and thus the proportion of sensitized guinea pigs corresponds to zero.

The first study on patients who developed anal dentition and treated with the composition of the present invention

Treatment with the composition of the present invention was performed on patients with acute anal dentition from 21 to 72 years (mean age 38.7 years). Treatment lasted for one month and was accomplished by topically applying dentures with a composition in gel cream form three times a day. Patients did not report any form of side effects.

After one month of treatment, there were complete relief of painful symptoms in 5 of 10 patients, and a significant reduction was observed in 4 other patients. Pain was measured using a Visual Analogue Scale (VAS), with an average VAS ranging from 9 to 3.25.

Complete scarring of the dentition was confirmed after 6 months of treatment in 6 of 10 patients.

At the end of local treatment in 7 patients, additional expansive treatments were needed and the treated patients were well received considering the fact that a marked improvement in their symptoms was observed.

In the second test 60 days later, complete scarring was observed in 9 of 10 patients.

The only patient who had not been completely cured continued the extended treatment for an additional 20 days and was found to have been completely treated at the next examination (ie, 90 days after the start of treatment).

The second study on patients who developed anal dentition and treated with the composition of the present invention

Ten patients with acute anal dentition were treated with the composition of the present invention in gel cream form.

Treatment consisted of a dose of 3 grams / day for 30 days or a dose of 3 grams / day for 50 days.

Patients were diagnosed with anal dentition through an anal examina- tion at an outpatient visit.

Patients were instructed on how to apply the gel cream, and when accompanied by constipation, stool softeners were administered for 30 or 50 days, respectively (FIBRAID, two Sachs per day).

Clinical follow-up, consisting of an examination and an anuscultation, was performed on days 10 and 30.

The primary goal is the resolution of symptoms reported during the first test.

The secondary goal is a macroscopic resolution of the dentition.

The characteristics of the patient and the results evaluated in the follow-up are summarized in Table 9.

Constipation is a symptom that occurs in about 70% of patients.

In 58% of the treated patients, an immediate effect was observed, namely a symptom resolution or pronounced improvement within 10 days after treatment, which increased to 75% at 30 days.

The dentition was macroscopically resolved in two patients who were treated within 10 days after symptom onset within one month.

The overall rate of need for additional treatment was 27%, with one patient missing on follow-up 50 days.

patient
N. Duration of symptoms until diagnosis Related constipation Related diarrhea Symptom Resolution 10 d Fix the teeth
10 d Symptom resolution
30 d Stiffness resolution 30 d gg The need for other treatments One 1 month + - + - + + - 2 15th + - + - + + - 3 3 months + - - - + - - 4 1 month - - + - + + - 5 20 days + - + - + + - 6 3 months + - - - - - + 7 4 months - + - - - - + 8 15th + - + - + + - 9 1 month - - + + + + - 10 7 days + - + + + + -

Claims (38)

A pharmaceutical composition for treating anal dementia comprising at least one hibiscus protein extract. The pharmaceutical composition according to claim 1, further comprising at least one beta-glucan or a salt thereof. 3. The pharmaceutical composition according to claim 1 or 2, wherein the anal dentition is acute or chronic. 3. The pharmaceutical composition according to claim 1 or 2, wherein the composition is combined with a method or protocol for anal dental treatment. 3. The pharmaceutical composition according to claim 1 or 2, wherein the hibiscus is Hibiscus esculentus. 3. The pharmaceutical composition according to claim 1 or 2, wherein the protein extract is derived from the seed of the hibiscus. 3. The pharmaceutical composition according to claim 1 or 2, wherein the protein extract is at least one protein fraction. 8. The pharmaceutical composition according to claim 7, wherein the protein fraction is a protein hydrolyzate. 9. The pharmaceutical composition according to claim 8, wherein the hydrolyzate is a mixture of oligopeptides. The pharmaceutical composition according to claim 1 or 2, wherein the protein extract of hibiscus is present in a concentration ranging from 0.1 to 10% by weight. 3. The pharmaceutical composition according to claim 2, wherein the at least one beta-glucan is carboxymethyl-beta-glucan or a salt thereof. 3. The pharmaceutical composition according to claim 2, wherein the beta-glucan is present in a concentration ranging from 0.004 to 0.4% by weight. 3. The pharmaceutical composition of claim 2, wherein the weight ratio of the at least one protein extract to the at least one beta-glucan is 10-50: 1. The composition according to any one of claims 1 to 3, which is selected from the group consisting of dimethicone or dimethylpolysiloxane, glycerin, almond oil, phenyl trimethicone, borage oil, oats extract or mucilage, panthenol, calendula extract, ethylhexyl glycerin, Wherein the pharmaceutical composition further comprises a modulator selected from the group consisting of prolyl glycols, aspartic acid, maltodextrin and glyceryl stearate. The composition of claim 1 or 2, wherein the surfactant is selected from the group consisting of cetyl alcohol, cetyl (20) OE or ceteth-20, stearyl (20) OE or stearase-20 and PEG- ≪ / RTI > The pharmaceutical composition according to claim 1 or 2, further comprising a preservative, an antioxidant, a binder, a stabilizer or a chelating agent. The pharmaceutical composition according to claim 1 or 2, which is formulated as a cream, a gel cream, a gel, an oil, an emulsion, a gel emulsion, an ointment, a spray, a suppository or a stick. A method for producing a pharmaceutical composition according to claim 2,
(i) melting the modifier or surfactant at a temperature in the range of from 70 to 90 DEG C;
(ii) mixing the solvent, modifier, chelating agent or stabilizing emulsifier with the molten raw material according to step (i);
(iii) adding at least one hibiscus extract to the mixture according to step (ii);
(iv) adding at least one beta-glucan to the mixture of step (iii). delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete